Triazabutadienes can be triggered to release a highly reactive diazonium species in a pH-dependent way when placed in acidic conditions. Electron-rich phenyl systems such as resorcinol or tyrosine residues can react with the diazonium compounds to form stable azobenzene products. Alterations of these triazabutadiene motifs allow for modification of functionality, solubility, and other molecular properties. For example, triazabutadienes can be modified to function as cross-linkers; cleavage of the cross-linker triazabutadiene can liberate the diazonium species, in some cases near a site of interest.
The present invention features triazabutadienes as cleavable cross-linkers, wherein the triazabutadienes allow for cross-linking with a secondary component via click chemistry (copper (I) catalyzed azide alkyne cycloaddition), e.g., “clickable” triazabutadienes. In some embodiments, the clickable triazabutadienes comprise or are linked to a first component (e.g., a protein, a drug, a surface, etc.) and via click chemistry said first component can be cross-linked to a second component (e.g., another protein, surface, etc.).
The present invention also features methods of producing said clickable triazabutadienes and methods of use of said clickable triazabutadienes. For example, the compositions of the present invention may be used as biological cross-linkers and methods of the present invention may be used for biological methods such as detecting protein-protein interactions, mapping drug-target interactions, discovering or characterizing host-pathogen interactions, etc. The present invention also features methods of cleaving said triazabutadienes, e.g., cleaving the clickable triazabutadienes that has undergone click chemistry and is in the cross-linking state. In some embodiments, cleavage of the cross-linking triazabutadiene liberates the diazonium species; thus, the present invention also features methods that feature diazonium reactions following cleavage of said linking triazabutadienes.